Inflammatory cytokines and stroke and its subtypes: a genetic correlation and two-sample Mendelian randomization study
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Published on: August 18, 2015
Yu Guo1, Huaiyu Sun1, Shuai Hou1
1Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.
Insights
Inflammatory markers like IL-4, IL-1β, and IL-12p70 influence stroke risk. This study used Mendelian randomization to identify causal links between 41 inflammatory factors and stroke subtypes, offering potential new treatment avenues.
Area of Science:
- Genetics and Molecular Biology
- Neurology
- Immunology
Background:
- The precise causal links between specific inflammatory factors and various stroke subtypes are not fully understood.
- Inflammation plays a recognized role in the pathophysiology of cerebrovascular diseases.
Purpose of the Study:
- To investigate the potential causal relationships between 41 inflammatory factors and the risk of stroke and its major subtypes (ischemic stroke and intracerebral hemorrhage).
- To leverage Mendelian randomization (MR) to analyze these associations using genome-wide association study (GWAS) data.
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was conducted.
- The inverse-variance weighted (IVW) method was the primary analytical approach.
- Sensitivity analyses were performed to ensure the robustness of the findings.
Main Results:
- Lower interleukin-4 (IL-4) levels were associated with an increased risk of overall stroke and ischemic stroke (IS).
- Higher levels of interleukin-1β (IL-1β) and IL-12p70 were linked to a greater risk of stroke and IS.
- Decreased IL-17 levels showed a potential association with a higher likelihood of intracerebral hemorrhage (ICH).
- Several other inflammatory factors, including vascular endothelial growth factor (VEGF), were also implicated in the risk of IS.
Conclusions:
- Inflammatory markers significantly impact stroke development.
- These findings suggest that specific inflammatory factors could serve as potential therapeutic targets for stroke prevention and treatment.
Introduction:
The causal relationship between inflammatory factors and stroke subtypes remains unclear. This study aimed to analyze the causal relationship between 41 inflammatory factors and these two factors using Mendelian randomization (MR).
Methods:
We performed a two-sample MR analysis to assess the causal effects of 41 inflammatory cytokines on stroke and its subtypes and conducted a genome-wide association study (GWAS) data. The inverse-variance weighted (IVW) method was adopted as the main MR method, and we performed a series of two-sample Mendelian randomizations and related sensitivity analyses.
Results:
The study indicated some suggestive evidences: using the IVW approach, we found that lower possible levels of IL-4 were positively associated with the occurrence of stroke (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88-0.99, p = 0.014), higher interleukin (IL)-1β, IL-12p70 levels may be positively correlated with the occurrence of stroke (OR = 1.09, 95% CI: 1.01-1.18, p = 0.027; OR = 1.08, 95% CI: 1.02-1.15, p = 0.015). For IS, results showed that lower levels of IL-4, tumor necrosis factor-related apoptosis-inducing ligand were positively associated with the occurrence of possible ischemic stroke (IS) (OR = 0.92, 95% CI: 0.87-0.98, p = 0.006; OR = 0.95, 95% CI: 0.91-1.00, p = 0.031), higher levels of IL-1β, IL-12p70 and vascular endothelial growth factor (VEGF) may be positively correlated with the occurrence of IS (OR = 1.09, 95% CI: 1.00-1.19, p = 0.042; OR = 1.07, 95% CI: 1.01-1.15, p = 0.035; OR = 1.06, 95% CI: 1.00-1.12, p = 0.034). Our findings suggest that decreased IL-17 levels could potentially be linked to a higher likelihood of intracerebral hemorrhage (ICH) (OR = 0.51, 95% CI: 0.28-0.93, p = 0.028). For subtypes of stroke, IS and ICH, higher levels of growth regulated oncogene-α, beta nerve growth factor, IL-18, macrophage colony-stimulating factor, and induced protein 10 upregulated the risk factors while lower levels of IL-2ra and IL-17 upregulated the risk factors.
Conclusion:
In summary, our research validated that inflammatory markers have a pivotal impact on the development of stroke and could potentially offer a fresh approach to treating this condition.
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